This proposal describes a 5 year program for academic career development for Noah Hillman who has completed a fellowship in Neontal-Perinatal medicine and is currently a fulltime faculty member of the division of Neonatology/Pulmonary Biology at CCHMC. The research will focus on the mechanisms of lung Injury caused by the resuscitation of preterms using preterm sheep models. This program will provide new evidence for resuscitation guidelines for preterm infants. The transition from a fetus to a newborn requires the initiation of breathing, clearance of fluid from airways, and ventilation of the distal airspaces. Ventilation of the preterm sheep during this transition leads to lung inflammation, cytokine induction, acute phase inflammatory changes, and airway injury. Lung injury from resuscitation may initiate bronchopulmonary dysplasia in extremely premature infants. We have previously used a fetal sheep model to evaluate the effects of resuscitation maneuvers on the lung. In this proposal we will test the hypothesis that ventilation of the surfactant-deficient, preterm lung causes small airway injury and initiates an IL-1 dependant inflammatory response. The specific aims include l) Regional and temporal differences in ventilator induced lung injury, 2)Role of IL-1 in resuscitation induced lung injury, and 3)Role of PEEP and tidal volume on resuscitation induced lung injury. The research will be conducted under the supervision of Drs. Jobe and Kallapur, who are both experts in lung inflammation and the use of preterm sheep models. The Children's Research Foundation and the Division of Pulmonary Biology provides an ideal setting in which to conduct the proposed research program because of the abundant resources and wide ranging expertise of a talented group of investigators. This proposal incorporates achievable goals that will provide important knowledge on the resuscitation of preterm infants. RELEVANCE (See instructions): Although the majority of preterm infants require some resuscitation at birth, little is known about how best to initiate ventilation while minimizing the risk of lung injury. Ventilation of the preterm infant at birth may contribute to BPD in premature infants. Using fetal sheep models of resuscitation, we can test the maneuvers performed routinely on preterm infants and make recommendations to decrease lung injury. (End of Abstract)